The study on the cellular growth and its regulation in female reproductive organs and related tumors, with the reference of sex-steroids

以性类固醇为参考的女性生殖器官及相关肿瘤细胞生长及其调控的研究

• 批准号: 09470356
• 负责人: TAMAYA Teruhiko
• 金额: $ 5.76万
• 依托单位: GIFU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-09470356/
• 关键词: female reproductive organ; tumors; stimulation and inhibition of growth; sex steroid; receptor; GnRH; エストロゲン受容体; スプライシング・バリアント; プロゲステロン受容体A型; プロゲステロン受容体B型; 受容体発現異常; GnRH受容体; Gタンパク; 女性生殖器腫瘍; 性ステロイドホルモン; GnRH・レセプター

The growth of the female reproductive organs and related tumors is diversely regulated by hormones (steroids and polypeptides) through binding their corresponding cellular receptors, which is thereafter associated with the biological eventsAs the advance in dedifferentiation and malignancy of the tumors, cellular expressions of decreasing SHBG, increasing estrogen receptor (ER) exon 5 delated splicing variant (dominant positively functional), and decreasing progesterone receptor A (transcriptionally inhibitory) appear as trends.ER β is expressed in 1 out of 100 ER αs in the normal uterine endometrium and in 1 out of 10 ER α in the normal ovary, yet the ER β expression becomes variably low to high in the malignant transformation, in which ER α-related action might be exaggerated. PR-B and ER α, which are associated with steroid-related growth, are over-expressed in the N1H3T3 cells, which form colonies and over-grow in the nude-mouse.GnRH and its receptor are expressed in the uterine endometrial and the ovarian cancers, yet a GnRH agonist occupies the receptor, coupled with Gi protein, resulting in the induction of dephospholyrase and lysophosphatidic acid dehydrase. A GnRH agonist induces apoptosis in the receptor carring tumors as well. Those might be related to the suppretion of tumor growth by a GnRH agonist.In the tumor cells, the cellular maturity process of GnRH is disturbed, whichi is related to the following evidence ; the pro-peptides of GnRH occupies the receptor, resulting the inhibition of cellular GnRH function which might be related the tumor growth.

女性生殖器官及相关肿瘤的生长受激素（类固醇和多肽）通过结合其相应的细胞受体而受到多种调节，从而与肿瘤去分化和恶性化进展、SHBG减少、雌激素受体（ER）外显子5延迟剪接变异体增加（显性正功能）的细胞表达等生物学事件相关。黄体酮受体A（转录抑制）呈下降趋势。正常子宫内膜ER αs表达率为1 / 100，正常卵巢ER α表达率为1 / 10，但在恶性转化中ER β表达由低到高变化，与ER α相关的作用可能被夸大。PR-B和ER α与类固醇相关生长相关，在N1H3T3细胞中过度表达，形成集落，在裸鼠体内过度生长。GnRH及其受体在子宫内膜和卵巢癌中均有表达，但GnRH激动剂占据受体，与Gi蛋白偶联，诱导去磷脂酶和溶血磷脂酸脱氢酶。GnRH激动剂也可诱导受体肿瘤细胞凋亡。这些可能与GnRH激动剂抑制肿瘤生长有关。在肿瘤细胞中，GnRH的细胞成熟过程受到干扰，这与以下证据有关：GnRH的前肽占据受体，抑制细胞GnRH功能，可能与肿瘤生长有关。

项目成果

Ryou Misao et al.: "Expression of oestrogen receptor α and β mRNA in corpus luteum of human subjects."Molecular Human Reproduction. 5(1). 17-21 (1999)

Ryou Misao 等人：“人类受试者黄体中雌激素受体 α 和 β mRNA 的表达”，《分子人类生殖》5(1) (1999)。

Fujimoto J,Tamaya T et al.: "Expression of oestrogen receptor-α and-β in ovarian endometriomata."Mol Hum Reprod. 5. 742-747 (1999)

Fujimoto J、Tamaya T 等人：“卵巢子宫内膜瘤中雌激素受体 -α 和 -β 的表达”，Mol Hum Reprod。5. 742-747 (1999)

Imai A,Tamaya T: "Vitam Horm vol.59 GnRH receptor and apoptotic signaling."Gerald Litwack ed, San Diego, Academic Press,. 378(1-33) (2000)

Imai A，Tamaya T：“Vitam Horm vol.59 GnRH 受体和细胞凋亡信号传导。”Gerald Litwack 编辑，圣地亚哥，学术出版社。

Fujimoto J,Tamaya T et al.: "Expression of progesterone receptor form A and B mRNAs in uterine leiomyoma."Tumor Biol. 19. 126-131 (1998)

Fujimoto J、Tamaya T 等人：“子宫肌瘤中孕酮受体 A 型和 B 型 mRNA 的表达。”肿瘤生物学。

A.Imai,T.Tamaya et al.: "GnRH analogue repairs reduced endometrial cell apoptosis in endometriosis in vitro."Am J Obstet Gynecol. 182. 1142-1146 (2000)

A.Imai、T.Tamaya 等人：“GnRH 类似物可在体外修复子宫内膜异位症中减少的子宫内膜细胞凋亡。”Am J Obstet Gynecol。